The goal of this project is to better understand the changes in cerebro-cerebellar brain function that occur after chronic alcoholism. Using verbal and spatial working memory as model paradigms for investigating cognitive- related cerebro-cerebellar function, our preliminary investigations have suggested that alcoholism can produce either decreases in activation or increases that may be compensatory in nature. We propose to further investigate alcohol-related changes in activation using event-related functional magnetic resonance imaging (fMRI) methods designed to shed more light on the nature of alcohol-induced neuropsychological deficits. Our working memory paradigm is comprised of 3 distinct task phases of encoding, maintenance, and retrieval of information. It has not been determined whether changes in brain activation observed thus far in alcoholics are derived from one or more of the cognitive demands occurring during these task phases. Specifically, differences in activation we have observed could be due to differences in the ability to acquire sensory input and encode verbal information (encoding), differences in rehearsal of information (maintenance), differences in the executive utilization of the maintained information (retrieval), or a combination of these three. We will use event-related fMRI to examine phase specific differences caused by alcoholism, and we will introduce phase- specific challenges to further examine process-specific changes in regional cerebro-cerebellar activation that differ between alcoholic and non-alcoholic subjects. We will also investigate possible dissociations of verbal and spatial working memory on alcohol-related changes in cerebro-cerebellar activation. Whereas spatial working memory in alcoholic subjects has revealed decreases in frontal lobe activation, verbal working memory has elicited left frontal and right cerebellar increases in activation. We propose to investigate whether these different patterns reflect differences in tasks across studies, differences in alcoholic populations, or differences in the effect of alcohol on neural substrates underlying verbal and spatial working memory. Finally, scans designed to measure blood flow, blood volume, and blood oxygenation will be used to determine to what extent BOLD signal differences in the populations are influenced by vascular and/or metabolic changes. These investigations will provide a better understanding of how chronic alcoholism changes brain function underlying cognition. PUBLIC HEALTH RELEVANCE: Chronic alcoholism is known to cause structural changes in the brain, but little is known about the effects of alcoholism on brain function underlying cognitive performance. The experiments in this proposal are designed to characterize, using functional MRI and tasks of verbal and spatial working memory, differences between alcoholics and non-alcoholics in brain function underlying these fundamental cognitive processes.